Incidence of Deep Vein Thrombosis in Restrained ... - Psychosomatics

Psychosomatics 2014:55:69–75

& 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Original Research Reports Incidence of Deep Vein Thrombosis in Restrained Psychiatric Patients Takuto Ishida, M.D., Takeshi Katagiri, M.D., Hiroyuki Uchida, M.D., Ph.D., Hiroyoshi Takeuchi, M.D., Ph.D., Hitoshi Sakurai, M.D., Koichiro Watanabe, M.D., Ph.D., Masaru Mimura, M.D., Ph.D.

Background: Although physical restraint is still used in psychiatric inpatient settings, it sometimes causes serious side effects, including deep vein thrombosis (DVT) and resulting pulmonary embolism. Objective: The aim of this study was to investigate the incidence of the DVT in restrained patients who were receiving routine prophylaxis and to identify the risk factors of this condition. Methods: This study was conducted at Sakuragaoka Memorial Hospital, Japan from December 2008 to September 2010. Inpatients who were restrained during the study period were included. All restrained patients wore graduated compression stockings and were recommended to receive subcutaneous injection of unfractionated heparin during the period of restraint unless it was contraindicated. When plasma D-dimer level at the time of removal of restraint was ≥ 0.50 μg/dL, the patients underwent a Doppler ultrasound scanning of their lower extremities to examine the presence of DVT. A multiple logistic

regression model was used to examine the effects of demographic and clinical characteristics on the incidence of DVT. Results: A total of 181 patients (98 men; mean ⫾ standard deviation age, 47.8 ⫾ 17.0 y) were included; DVT was detected in 21 patients (11.6%). A longer duration of restraint (odds ratio ¼ 9.77, 95% confidence interval ¼ 1.56–61.03, p ¼ 0.015), excessive sedation (odds ratio ¼ 4.90, 95% confidence interval ¼ 1.33–18.02, p ¼ 0.017), lower antipsychotic dosage (odds ratio ¼ 0.05, 95% confidence interval ¼ 0.005– 0.57, p ¼ 0.016), and recent medical hospitalization (odds ratio ¼ 11.44, 95% confidence interval ¼ 2.13– 61.47, p ¼ 0.004) were significantly associated with the incidence of DVT. Conclusion: The incidence of DVT in restrained psychiatric patients was not low in spite of prophylaxis. These findings emphasize the importance of regular screening of and thorough assessments of DVT, especially in restrained psychiatric patients. (Psychosomatics 2014; 55:69–75)

P

proximal vein, PE reportedly occurs in up to 50% of the patients.4 Immobilization is an established risk

hysical restraint is still used in psychiatric inpatient settings for safety reasons although it does raise ethical concerns; moreover, this practice could cause serious adverse events, including unexpected death.1,2 Pulmonary embolism (PE) has been considered to be one of the causes of unexpected death when patients are restrained.2 PE commonly derives from deep vein thrombosis (DVT) of the lower extremities.3 Most DVTs originate in the calves, and 80% of distal DVTs are known to resolve spontaneously.4 However, 20% of distal DVTs can extend into the proximal vein (i.e., popliteal vein or higher). Once DVTs reach a

Psychosomatics 55:1, January/February 2014

Received February 15, 2013; revised March 3, 2013; accepted April 1, 2013. From Department of Psychiatry, Sakuragaoka Memorial Hospital, Tokyo, Japan; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan. Send correspondence and reprint requests to Takuto Ishida, M.D., Department of Psychiatry, Sakuragaoka Memorial Hospital, 1-1-1 Renkouji, Tama-shi, Tokyo, 206-0021, Japan; e-mail: [email protected] & 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

www.psychosomaticsjournal.org

69

Deep Vein Thrombosis in Restrained Psychiatric Patients factor for DVT; hence, physical restraint clearly increases the risk of PE. Indeed, fatal PE in restrained patients has often been reported.3,5 To effectively prevent PE in restrained patients, it is critically important to detect DVTs of the lower extremities and provide appropriate treatment. DVT has been reported to occur in 10% to 40% of hospitalized patients with a physical morbidity.6 The American College of Chest Physician conference has provided the guidelines for prevention of DVT in medically ill patients, in which prophylactic use of unfractionated heparin (UFH) or low-molecularweight heparin is indicated for high-risk patients.7 Although no mention of psychiatric inpatients is included in these guidelines, other guidelines recommend the assessment of patients' risk level and the use of various prophylactic measures, including graduated compression stocking, UFH, and low-molecularweight heparin, in psychiatric inpatients.8,9 However, risk factors of DVT have not systematically been investigated in psychiatric inpatients. Moreover, there has been no systematic survey of the incidence of DVT in psychiatric inpatients. The incidence of DVT is likely to be high in this population, especially in restrained patients, given their reduced physical activity. Therefore, we conducted a retrospective chart review to investigate the incidence of DVT in restrained patients who were receiving routine assessment of, and prophylaxis for, DVT. In addition, risk factors for DVT were investigated. METHODS This study was conducted at Sakuragaoka Memorial Hospital, a tertiary psychiatric hospital in Tokyo, Japan. This hospital has 9 inpatient wards (an acute phase unit, a dementia unit, a unit for physical conditions, a unit for drug dependence, and 5 units for chronic patients), and the number of admissions is approximately 700 patients per year. In this hospital, routine prophylaxis for DVT has been employed for physically restrained patients since December 1, 2008. Restrained patients were identified from electronic medical records of all inpatients during the study period. The duration of restraint was recorded in the electronic medical records. The data of the first episode of restraint were collected when patients received it more than once during the study period. A systematic chart review of inpatients with any psychiatric 70


diagnosis who were restrained anytime between December 1, 2008 and September 30, 2010 was performed. This study was approved by the institutional review board of Sakuragaoka Memorial Hospital and exempted from the requirement for informed consent because the study involved deidentified data acquired during routine care. All restrained patients wore graduated compression stockings and had a recommendation to receive subcutaneous injection of UFH 5000 IU b.i.d. during the period of restraint unless it was contraindicated. Patients whose duration of restraint was shorter than 12 hours did not receive any UFH, whereas those whose duration of restraint was 12 or more hours received UFH twice daily. A plasma D-dimer level was evaluated when the restraint was removed. When the plasma D-dimer level was 0.50 μg/dL or higher, the patients underwent a Doppler ultrasound scanning of their lower extremities to examine the presence of DVT. Given that a negative predictive value of D-dimer level of o 0.50 μg/dL for DVT is reportedly 99%, patients who showed a D-dimer level o 0.50 μg/dL were considered to be free of DVT.10 The following demographic and clinical information was collected: age, sex, duration of restraint, medical history, comorbid physical illnesses, and antipsychotic prescriptions. Daily doses of antipsychotics on the day of initiation of restraint, including depot antipsychotics, were converted to chlorpromazine equivalents.11 For subjects who were receiving more than 1 antipsychotic drug, a sum of chlorpromazine equivalents for all prescribed antipsychotic medications was calculated. Subjects who received o 300 mg/d and ≥ 600mg/d chlorpromazine equivalents were considered to belong to low- and high-dose groups, respectively, whereas others were sorted to a standard dose group, in accordance with the Schizophrenia Patient Outcomes Research Team Treatment Recommendations.12 We also examined if the patients were excessively sedated or not during the restraint because we expected that a lack of voluntary movements from such a condition would increase the risk of DVT. Statistical analyses were carried out, using the SPSS Version 17.0 (SPSS Inc., Chicago). To examine the effects of various characteristics on the incidence of DVT, a multiple logistic regression model was used with the following variables: antipsychotic dosage (i.e., high-, standard-, or low-dose group), duration Psychosomatics 55:1, January/February 2014

Ishida et al. of restraint (i.e., o24, ≥ 24 and o72, or ≥ 72 h), presence of excessive sedation, employment of restraint of the lower extremities, age group (i.e., o65 or ≥ 65 y), type of inpatient ward (i.e., acute unit or others), and hospitalization for physical comorbidities within the previous 90 days. We also used a multiple logistic regression model in a subgroup of patients who showed a D-dimer level of ≥ 0.50 μg/dL, using with same variables. A p value o0.05 was considered statistically significant and all tests were 2-tailed. RESULTS A total of 190 patients were restrained during the study period. Nine patients were excluded because they did not undergo timely ultrasound scanning even though their D-dimer levels were higher than 0.5 μg/dL. Thus, a total of 181 patients were included in the acute phase unit. Three-fourths of the restraints were applied on 54.1% of the restrained patients (N ¼ 98) were men, and their mean ⫾ standard deviation age was 47.8 ⫾ 17.0 years. Their ICD-10 diagnoses were as follows: F0 (organic, including symptomatic, mental disorder) ¼ 7; F1 (mental and behavioral disorder because of psychoactive substance use) ¼ 18; F2 (schizophrenia, schizotypal, and delusional disorders) ¼ 115; F3 (mood disorders) ¼ 27; F4 (neurotic, stress-related, and somatoform disorders) ¼ 2; and F6 (disorders of adult personality and behavior) ¼ 12. Mean ⫾ standard deviation chlorpromazine equivalents was 597.0 ⫾ 528.2 mg/d where 61, 49, and 71 patients were grouped into the low-, middle-, and high-dose groups, respectively. Fourteen patients were hospitalized because of physical illnesses within 90 days before their restraint. There was no patient who had a history of DVT/PE or chronic heart failure. Moreover, no patient was suffering from an acute exacerbation of chronic obstructive pulmonary disease. In addition, there were no pregnant patients. Only 1 patient had a malignancy, 2 patients underwent a recent surgery, and 3 patients had a history of stroke with hemiparesis; 63.5% of patients received UFH. One patient experienced a side effect: minor nasal bleeding. The mean ⫾ standard deviation duration of restraint was 74.1 ⫾ 93.6 hours. Seventy-two patients showed a plasma D-dimer level of ≥ 0.50 μg/dL and therefore received a Doppler ultrasound scanning of their lower extremities. DVT was detected in 21 Psychosomatics 55:1, January/February 2014

patients (11.6%); all cases were asymptomatic and accompanied by a with DVT at a distal vein (i.e., lower than the popliteal vein). A multiple logistic regression model demonstrated that excessive sedation, a longer duration of restraint, lower antipsychotic dosage, and hospitalization for physical comorbidities within the previous 90 days were significantly associated with the increased incidence of DVT (Table 1). In a subgroup of patients who showed a D-dimer level ≥ 0.50 μg/dL, a multiple logistic regression model demonstrated that excessive sedation, lower antipsychotic dosage, and the presence of restraint of lower extremities were significantly associated with the increased incidence of DVT (Table 2). DISCUSSION The main findings of this study are 2-fold: (1) the incidence of DVT in restrained psychiatric inpatients was 11.6% even with the prophylactic use of UFH, and (2) excessive sedation, a longer duration of restraint, hospitalization for physical comorbidities within previous 90 days, and lower antipsychotic doses were significantly associated with an increased incidence of DVT. To our knowledge, this is the first systematic survey on the risk factors for DVT in psychiatric settings. The annual incidece rate of DVT in the general population has been reported to be 1 per 1000.13 Although the use of antipsychotics is known to increase the risk for DVT (odds ratio ¼ 1.32), the incidence of 11.6% that we observed in the present study appear high.14 The strength of the present study is the use of a thorough assessment of DVT with a Doppler ultrasound scanning of patients' lower extremities, which is especially important for morbid conditions that are often asymptomatic. In fact, approximately 70% to 80% of DVTs of hospitalized medical patients are asymptomatic.15 According to one recent report, 65 secluded patients, a majority of whom received physical restraint as well, were administered low-molecular-weight heparin at the time of seclusion; none of them experienced any DVT.16 However, as the diagnosis of DVT was solely based on descriptions in charts in that study, the incidence of DVT was very likely to be underestimated. Indeed, DVT is often overlooked because psychiatric patients are often unaware of any leg symptoms because of their psychiatric symptoms and sedation, which results www.psychosomaticsjournal.org

71

Deep Vein Thrombosis in Restrained Psychiatric Patients TABLE 1.

Clinical Demographics and Incidence of DVT

Variables Sex Male Female

DVT positive

Odds ratio

95% CI

p Value

12/98 (12.2%) 9/83 (10.8%)

1 1.36

0.41–4.45

0.61

15/151 (9.9%) 6/30 (20.0%)

1 1.60

0.39–6.524

0.51

4/65 (6.1%) 7/64 (10.9%) 10/52 (19.2%)

1 3.21 9.77

0.64–16.09 1.56–61.03

0.157 0.015*

Usage of UFH Absent Present

7/66 (10.6%) 14/115 (12.1%)

1 0.64

0.16–2.51

0.52

Restraint of lower extremities Absent Present

15/132 (11.3%) 6/49 (12.2%)

1 3.92

0.40–6.23

0.07

6/131 (4.5%) 15/50 (30.0%)

1 4.90

1.33–18.02

0.017*

Antipsychotic dosage, CPZE mg/d o300 13/61 (21.3%) ≥300 and o600 7/49 (14.3%) ≥600 1/71 (1.4%)

1 0.79 0.05

Age (years) o65 ≥65 Duration of restraint, h o24 24–72 ≥72

Excessive sedation Absent Present

0.22–2.81 0.005–0.57

0.71 0.016*

Hospitalization for physical comorbidities within previous 90 days Absent 15/167 (9.5%) 1 Present 6/14 (42.9%) 11.44

2.13–61.47

0.004*

Type of inpatients ward Acute phase unit Other

0.19–3.01

0.72

13/137 (9.0%) 8/44 (18.2%)

1 0.77

CI ¼ confidence interval; DVT ¼ deep vein thrombosis; UFH ¼ unfractionated heparin; CPZE ¼ chlorpromazine equivalents. p Values with significant results are labeled with an asterisk.

in PE as the first clinical manifestation of DVT in restrained patients.5 Consistent with this notion, 97% of 38 DVTs that were detected by ultrasound scanning were not accompanied with any physical symptom in the previous study; moreover, none of the DVTs that were found with a Doppler ultrasound scanning was symptomatic in the present study.17 Immobilization is an established risk factor of DVT and PE; it is reasonable that a longer duration of restraint was significantly associated with the higher incidence of DVT.1 Consistently, in the case series by Dickson and Pollanen, the restrained period for patients who suffered PE was as long as 3 to 15 days, and proximal DVTs were found in patients who were restrained for longer than 5 days in another survey.5,18 Excessive sedation was another risk factor of DVT in the 72


present study. Patients are often given a high amount of sedative psychotropic medications in real-world clinical settings in case they are extremely agitated and psychotic, although such treatment has been criticized. Such sedated patients rarely move their body, including their lower extremities, which may hamper a spontaneous resolution of DVT and rather keep the DVT growing. In contrast, agitated patients move their extremities excessively even when restrainted, which may be protective against the development of DVT. These findings underscore the critical need for thorough assessments of DVT, using Doppler ultrasound scanning, especially in high-risk psychiatric patients. The use of lower doses of antipsychotics was paradoxically related to a greater incidence of DVT. One possible explanation may be the potential effects Psychosomatics 55:1, January/February 2014

Ishida et al. TABLE 2.

Clinical Demographics and Incidence of DVT in a Subgroup of Patients With a Plasma D-dimer Level 40.50 μg/dL Odds ratio

95% CI

p Value

Variables

DVT positive

Sex Male Female

12/43 (27.9%) 9/29 (31.0%)

1 2.78

0.61–12.39

0.19

Age o65 ≥65

15/56 (26.8%) 6/16 (37.5%)

1 1.17

0.25–5.41

0.84

Duration of restraint, h o24 24–72 ≥72

4/17 (23.5%) 7/25 (28.0%) 10/30 (33.3%)

1 1.62 2.56

0.28–9.59 0.32–19.99

0.59 0.37

Usage of UFH Absent Present

7/25 (28.0%) 14/47 (12.1%)

1 0.51

0.09–2.99

0.46

Restraint of lower extremities Absent Present

15/59 (25.4%) 6/13 (46.2%)

1 11.75

1.46–94.91

0.021*

Excessive sedation Absent Present

6/43 (1.4%) 15/29 (51.7%)

1 5.61

1.05–30.0

0.044*

Antipsychotic dosage, CPZE mg/d o300 13/31 (41.9%) ≥300 and o600 7/20 (35.0%) ≥600 1/21 (4.8%)

1 0.57 0.06

0.10–3.18 0.004–0.96

0.52 0.047*

Hospitalization for physical comorbidities within previous 90 days Absent 16/63 (25.4%) 1 Present 5/9 (55.6%) 5.81

0.89–37.79

0.065

Type of inpatients ward Acute phase unit Other

0.07–3.27

0.45

13/51 (25.5%) 8/21 (38.1%)

1 0.48

CI ¼ confidence interval; DVT, deep vein thrombosis; UFH, unfractionated heparin; CPZE, chlorpromazine equivalents. p Values with significant results are labeled with an asterisk.

of physical comorbidities, including infection and recent surgery, which are reportedly risk factors for DVT.7 In fact, the number of patients who suffered from physical comorbidities was highest in the lowdose group (32.8%), compared with the middle- and high-dose groups (16.3% and 8.5%, respectively). Clinicians tend to prescribe lower doses to patients with comorbid conditions who are especially sensitive to antipsychotic-induced sedation. Still, given methodologic limitations, as described later, these preliminary findings need to be confirmed by future investigations. There are several limitations to be noted in this study. First, although this is the largest study on the survey of DVT in psychiatric patients, the sample size is still small. Second, approximately one-third of the Psychosomatics 55:1, January/February 2014

patients did not receive the UFH prophylaxis because of clinical and administrative reasons, such as a lack of laboratory data and a short duration of restraint; therefore, the incidence of DVT should be interpreted with caution. Third, we may have underestimated the incidence of DVTs because patients who showed a D-dimer level of o0.5 μg/dL did not undergo a Doppler ultrasound scanning. Although the negative predictive value of the D-dimer level is reportedly as high as 99%, this possibility of underestimation cannot be entirely rejected.10 Fourth, although we acknowledged the relevance of inclusion of physical comorbidities as a risk factor in the analysis, the very small number of patients who had each physical illness precluded such an analysis. Moreover, the use of oral contraceptives and hormone replacement therapy and www.psychosomaticsjournal.org

73

Deep Vein Thrombosis in Restrained Psychiatric Patients smoking status were not documented in the charts and were not taken into account. Fifth, we did not include psychiatric diagnoses in the analysis because the number of patients with each diagnosis was very small. In light of the reported increase of D-dimer level in patients with acute psychosis, further investigations on this issue are warranted. Sixth, the presence of excessive sedation was assessed based on chart reviews.18 Thus, in light of those limitations, the findings in the present study need to be replicated in larger, more methodologically rigorous studies. In conclusion, the incidence rate of DVT was more than 10% in patients who were restrained even though they received prophylaxis with UFH. These findings emphasize the importance of regular screening of, and thorough assessments for DVT, using an appropriate devise such as Doppler ultrasound scanning, in the high-risk group of restrained psychiatric patients. Furthermore, the duration of restraint and sedation should be minimized as much as possible to decrease the risk of DVT. Given the paucity of the data on this clinically relevant issue, further investigations are needed to devise efficient screening methods for the detection and prevention of DVT. CONTRIBUTORS All authors contributed to and approved the design and the protocol of the study, the literature searches, and analyses. Dr. Ishida wrote the first draft of the article, and all authors contributed to and approved the final draft of the article. PREVIOUS PRESENTATION A part of the data was presented at the 106th annual meeting of the Japanese Society of Psychiatry and Neurology, Hiroshima, Japan, May 22, 2010.

Dr. Uchida has received grants from Pfizer, Astellas Pharmaceutical, Eisai, Otsuka Pharmaceutical, Pharmaceutical, GlaxoSmithKline, Shionogi, and Dainippon Sumitomo Pharma, Eli Lilly, Mochida Pharmaceutical, Meiji-Seika Pharma, Janssen Pharmaceutical, and Yoshitomi Yakuhin and speaker's honoraria from Otsuka Pharmaceutical, Janssen Pharmaceutical, Novartis Pharma, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Dainippon Sumitomo Pharma, and Janssen Pharmaceutical for the past 3 years. Dr. Takeuchi has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology and Astellas Foundation for Research on Metabolic Disorders, speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKlein, Janssen Pharmaceutical, Meiji Seika Pharma, and Otsuka Pharmaceutical, and manuscript fees from Dainippon Sumitomo Pharma for the past 3 years. Dr. Watanabe has served on the advisory board of Dainippon Sumitomo Pharma, Eli Lilly, Janssen, Otsuka and Schering-Plough and received speaker's honoraria from Asahi Kasei, Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Otsuka, and Pfizer for the past 3 years. Dr. Mimura has received grants, or consultant fees from Eisai, Astellas Pharma, GlaxoSmithKline and Meiji, and received speaker's honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji, Otsuka Pharmaceutical, Pfizer, and Yoshitomi Yakuhin for the past 3 years. Other authors have nothing to disclose. The authors gratefully acknowledge Drs. Satoru Iwashita, Sachiko Irie, and Yuki Kikuchi for their continuous support and insightful advice. Disclosure: The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article.

References 1. Steinert T, Lepping P, Bernhardsgrutter R, et al: Incidence of seclusion and restraint in psychiatric hospitals: a literature reviews and survey of international trends. Soc Psychiat Epidemiol 2010; 45:889–897 2. Mohr WK, Pettii TA, Mohr BD: Adverse effects associated with physical restraint. Can J Psychiatry 2003; 48:330–337 3. Victor F: Acute pulmonary embolism. N Engl J Med 2008; 358:1037–1052

74


4. Clive K: Natural history of venous thromboembolism. Circulation 2003; 107:I-22–I-30 5. Dickson BC, Pollanen MS: Fatal thromboembolic disease: a risk in physically restrained psychiatric patients. J Forensic Leg Med 2009; 16:284–286 6. Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, Geerts WH: Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med 2001; 161:1268–1279


Ishida et al. 7. Geerts WH, Bergqvist D, Pineo GF, et al: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest 2008; 133:381S–453S 8. Maly R, Masopust J, Hosak L, Konupcikova K: Assessment of risk of venous thromboembolism and its prevention in psychiatric patients. Psychiatry Clin Neurosci 2008; 62:3–8 9. Japanese Society of General Hospital Psychiatry: Guideline for Prevention of Deep Venous Thrombosis. Tokyo: Seiwa Press; 2006 [in Japanese] 10. Wells PS, Anderson DR, Rodger M, et al: Evaluation of D-dimer in the diagnosis of suspected deep vein thrombosis. N Engl J Med 2003; 349:1227–1235 11. Inagaki A, Inada T, Fujii Y: Dose Equivalents of Psychotropic Drugs. Tokyo: Seiwa Press; 1999 [in Japanese] 12. Lehman AF, Steinwachs DM: Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull 1998; 24:1–10 13. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ: Trends in the incidence of deep vein


14.

15.

16.

17.

18.

thrombosis and pulmonary embolism: a 25-year populationbased study. Arch Intern Med 1998; 158:585–593 Parker C, Coupland C, Hippisley-Cox J: Antipsychotics drugs and risk of venous thromboembolism: nested casecontrol study. Br Med J 2010; 21:c4245 Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA: Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146:278–288 De Hert M, Einfinger G, Scherpenberg E, Wampers M, Peuskens J: The prevention of deep venous thrombosis in physically restrained patients with schizophrenia. Int J Clin Pract 2010; 64:1109–1115 Matsunaga R, Gomibuchi T, Wakejima T, Okazaki Y: Clinical study of venous thromboembolism in psychiatric inpatients subjected to physical restraints. Seishin Igaku 2009; 51:739–746 [in Japanese] Masopust J, Maly R, Andrys C, Valis M, Bazant J, Hosak L: Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study. BMC Psychiatry 2011; 13:2, http://dx.doi.org/10.1186/ 1471-244X-11-2


75